B-cell-secreted Toxins Kill Neurons and Myelin-Producing Cells, MS Study Reports
B-cells of patients with relapsing-remitting multiple sclerosis (RRMS) secrete substances that are toxic to both neurons and neuron-protecting myelin-forming cells, causing both kinds to die, according to a study.
Despite analyses of numerous inflammatory and other factors believed to drive MS processes, researchers were unable to identify the molecules that are toxic, however.
Dr. Robert Lisak of Wayne State University in Detroit, Dr. Amit Bar-Or of McGill University in Montreal and their teams are now working on identifying the factor, and learning if the process is also involved in progressive MS.
Their study, “B-cells from patients with multiple sclerosis induce cell death via apoptosis in neurons in vitro,” was published in the Journal of Neuroimmunology.
It demonstrated that B-cells gathered from the blood of RRMS patients killed lab-grown neurons and oligodendrocyte cells, which form myelin, a protecting coating for nerve cells. Deterioration of the myelin coating and the death of neurons are hallmarks of MS.
An earlier study the team conducted indicated that B-cells from MS patients could kill oligodendrocytes. But since the experiments involved only three patients and three controls, the team scaled up their experiments to include 13 patients and an equal number of controls.
Both rat and human neurons died when mixed with MS-derived B-cells. In contrast, B-cells from healthy people had little or no impact on the survival of the brain cells.
Researchers also discovered that the secreted toxic molecules had no impact on other types of central nervous system cells — astrocytes and microglia. The toxins killed only neurons and myelin-producing cells.
The B-cells triggered a process called apoptosis, or programmed cell death, researchers said. This is basically a suicide program. It tells a cell to die when exposed to stressful factors or toxins. The process differs from cell disintegration.
Despite thoroughly screening about 40 inflammation-related substances, researchers were unable to identify any factors that caused the cells to die.
The National MS Society and the Research Foundation of the MS Society of Canada funded the research, which the U.S. society highlighted in a news release. In the newest phase of the study, researchers will try to learn more about the processes underlying neuron and myelin-related cell deaths and identify the factors responsible.
In addition to testing B-cells from progressive MS patients, the team will examine patients with other autoimmune conditions to see if the process is unique to MS or not.
Researchers increasingly realize that B-cells are important to MS processes. This observation was underscored by U.S. regulators’ approval of the B-cell depleting therapy Ocrevus (ocrelizumab) at treatment for both relapsing and primary progressive MS.